Citalopram is a well known antidepressant drug that has now been on the market for some years and has the following structure:

It is a selective, centrally acting serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, accordingly having antidepressant activities. The antidepressant activity of the compound has been reported in several publications, eg. J. Hyttel, Prog. Neuro-Psychopharmacol. & Biol. Psychiat., 1982, 6, 277-295 and A. Gravem, Acta Psychiatr. Scand., 1987, 75, 478-486. The compound has further been disclosed to show effects in the treatment of dementia and cerebrovascular disorders, EP-A 474580.
Citalopram can be prepared by several disclosed methods. A method and an intermediate for the preparation of citalopram were described in U.S. Pat. No. 4,650,884. Commercially useful processes are disclosed in International patent application Nos. WO 98019511, WO 98019512 and WO 98019513.
With respect to the above methods for the preparation of citalopram, the process comprising exchange of the 5-bromo group with cyano proved not to be very convenient in commercial scale, since the yield was rather low, the product was impure and, in particular, since it was difficult to separate the resulting citalopram from the corresponding 5-bromo compound.
It has now been found that in a new process for the preparation of citalopram, this key intermediate may be obtained in a high yield as a very pure product by a new catalytic process in which a halogen or a group of the general formula CF3—(CF2)n—SO2—wherein n is any suitable whole number between 0 and 4, situated in the 5-position of a 3-H-isobenzofuran-1-one, is exchanged with a cyanide group. By obtaining the correct cyanide substitution at an early stage of the citalopram synthesis, the extensive work up of the old cyanide exchange processes of the previous described processes is avoided. The intermediates of the presently described process are easily purified and obtained in very high yields. The key intermediate is then subjected to two successive Grignard reactions, i.e. with 4-fluorophenyl magnesium halogenide and N,N-dimethylaminopropyl magnesium halogenide, respectively, whereby citalopram is obtained.
The preparation of the key intermediate of the invention is described earlier in J. Chem. Soc., 1931, 867 and by Tiroflet, J. in Bull. Soc. Sci. Betagne, 26, 35, 1951. The process for preparation of the compound is a three step synthesis starting from 5-nitro-phtalimide with low yields, especially in the last step of the synthesis.